In general, nanoparticle-based drug delivery systems are of interest in, inter alia, controlled release of drugs, delivery of anticancer drugs and imaging agents to tumors, tuberculosis treatment and as non-viral gene delivery vehicles. Some important advantages of nanoparticles in drug delivery systems are greater solubility, high stability, high carrier capacity, incorporation of biodegradable hydrophilic/hydrophobic substances and different ways of administering the drug including oral, injection, and inhalation methods. These desirable properties can improve drug bioavailability and patient compliance by reduced drug administration frequency.
In some drug delivery systems, each drug has a concentration range providing optimal therapeutic effects. When the concentration falls out of this range (either higher or lower), it may cause toxic effects or become therapeutically ineffective. Therefore, it can be desirable to release the drug from a polymer carrier in a sustained or a controlled manner. In general, a polymer carrier can also provide protection for fragile drugs (e.g., proteins and peptides) from hydrolysis and degradation. Protection from stomach acids is a good example since even small drug molecules such as erythromycin can be irritating to the gastric mucosa.
Lai et al. (“Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues,” Adv. Drug Deliv. Rev., 61 (2):158-171 (2008)) recently demonstrated that nanoparticles, if sufficiently coated with a muco-inert polymer such as lower molecular weight PEG, can rapidly traverse physiological human mucus with diffusivities almost as high as those in pure water. This finding suggests that it is possible to engineer (e.g., coat) nano-sized drug particles to overcome the mucus barrier, allowing sustained drug delivery to specific cells in the body at mucosal surfaces and provide improved efficacy and reduced side effects for a wide range of therapeutics.
In general, the potential for nanoparticles to revolutionize drug delivery systems is large. However, a number of problems need to be overcome including, for example, continuously layering and coating nanoparticles with polymeric materials to achieve time release, protecting them from stomach acids and being trapped by a mucus barrier, or preventing immune cells (macrophages) from engulfing and eliminating the nanoparticles circulating in the bloodstream. Nanoparticle surface coating or tailoring can also provide a variety of desirable properties in physical, optical, electronic, and chemical applications.
Conventional methods for coating or encapsulating micron-sized and nanoparticles utilize dry or wet approaches. For example, Wang et al. (“Polymer Coating/encapsulation of Nanoparticles using a Supercritical Anti-solvent Process,” J. Supercritical Fluids, 28, 84 (2004)) has summarized some of these approaches: dry methods include physical vapor deposition, plasma treatment, chemical vapor deposition, and pyrolysis of polymeric organic materials; wet methods cover sol-gel processes, emulsification and solvent evaporation techniques. Supercritical fluid processes such as rapid expansion of supercritical solutions (RESS), supercritical anti-solvent (SAS), and gas anti-solvent (GAS) processes employing supercritical CO2 are alternative methods for nanoparticle coating or encapsulation of ultrafine particles. For example, Yue et al. (“Particle Encapsulation with Polymers via in-situ Polymerization in Supercritical CO2”, Powder Technology, 146 (1-2), 32 (2004)) encapsulated hydrocortisone with polyvinylpyrrolidone (PVP) by in situ dispersion polymerization in supercritical CO2.
These processes have many shortcomings. Some processes, e.g., supercritical CO2-based processes (“SmCO5/CU Particles Elaboration using a Supercritical Fluid Process”, J. Alloys Compounds, 323, 412 (2001)), require demanding operating conditions (pressure about 190 MPa); SAS processes require significantly lower pressure about 10 MPa which is still high. RESS processes (e.g., Kim et al., “Microencapsulation of Naproxen using Rapid Expansion of Supercritical Solutions”, Biotechnol. Prog. 12, 650 (1996)) encounter low polymer solubility in supercritical CO2 at lower temperatures (less than 80° C.) and can use very few polymers which may lack bio-degradability or time release due to their limited CO2 solubility. Most of these techniques are also batch processes.
Fluidized bed-based processes (e.g., Tsutsumi et al. “A Novel Fluidized-bed Coating of Fine Particles by Rapid Expansion of Supercritical Fluid Solutions”, Powder Technol., 85, 275 (1995)), which can be continuous, face problems due to nanoparticle fluidization difficulties caused by van der Waals and other interparticle forces. In such processes, scale-up is also quite demanding. Nanoparticles, which tend to agglomerate rapidly in the dry state because of their large interparticle forces due to their small size, will typically only accentuate these problems when they are coated with polymers via precipitation/crystallization, etc.
Scale-up problems in conventional batch crystallizers which are usually stirred vessels include the problems of imperfect mixing and non-uniform conditions leading to a broad crystal size distribution (CSD). New monitoring techniques (e.g., Gron et al., “In-Process ATR-FTIR Spectroscopy for Closed-loop Supersaturation Control of a Batch Crystallizer Producing Monosodium Glutamate Crystals of Defined Size,” Ind. Eng. Chem. Res., 42, 198 (2003)) can lead to better prediction and control of the applied supersaturation in crystallizers. However, well-mixed crystallizers are intrinsically inclined toward a spectrum of local conditions in time and space and consequently a relatively broad CSD. To overcome these problems, a novel crystallizer design based on a hollow fiber device has been proposed (Zarkadas et al., “Solid Hollow Fiber Cooling Crystallization”, Ind. Eng. Chem. Res., 43, 7163 (2004)).
Thus, an interest exists for improved systems and methods for continuous polymer coating of particles (e.g., nanoparticles). These and other inefficiencies and opportunities for improvement are addressed and/or overcome by the assemblies, systems and methods of the present disclosure.